基于潜在药效物质组的中药注射剂PK-BN-PD模型的构建与应用

项目名称： 基于潜在药效物质组的中药注射剂PK-BN-PD模型的构建与应用

项目编号： No.81503244

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘颖

作者单位： 北京中医药大学

项目金额： 18万元

中文摘要： 本课题针对中药质量控制指标难以表征中药整体药效的科学问题，创新性地提出潜在药效物质组（EMM）的概念，用以表征参与中药整体药效的中药原型成分及其代谢物质组。与传统方法比较，这种方法具有在整体/复方给药基础上从复杂体系中快速准确确定中药质量控制指标的优势。.本课题首次应用贝叶斯网络（BN）技术构建中药代谢/效应（PK/PD）模型，开展苦碟子注射液干预大鼠脑缺血再灌注的EMM的筛选以及基于EMM和体内多成分相互作用的质量控制指标的筛选研究。应用UPLC-MS/MS测定MCAO再灌注模型大鼠血液或脑组织中苦碟子多成分的浓度，以炎症细胞因子和神经递质的浓度变化作为药效指标，构建基于PK-BN-PD筛选苦碟子注射液的EMM和质量控制指标的新策略。课题的完成，将为基于中药整体药效的中药质量控制指标的快速确定提供参考模式，为中药质量评价体系的建立提供新的思路。

中文关键词： 潜在药效物质组；中药注射剂；药物代谢动力学-药效动力学；贝叶斯网络；中药质量控制指标

英文摘要： Based on a scientific issue that the quality control components of traditional Chinese medicine（TCM）is difficult to characterize the overall efficacy of TCM, the concept of the potential efficacy material markers (EMM) was introduced, and EMM mainly included prototype components and their metabolites groups which participating efficacy of TCM. Compared with traditional methods, this method has the advantage in quickly and accurately determining on quality control components from complex system after administration of TCM..In this study, Kudiezi injection was chosen as research vector. On the basis of preliminary chemical constituents and pharmacological studies, the first application of Bayesian networks (BN) technology to build TCM metabolism/effect (PK/PD) model. The research was developed for screening the EMM of Kudiezi injection intervention focal cerebral ischemia reperfusion and for screening quality control components basing of EMM and multi-component interactions in vivo. UPLC-MS/MS was applied to determination of multi-component concentrations in MCAO and reperfusion rat brain tissue or in blood. Changes in concentration by inflammatory cytokines and neurotransmitters as efficacy indicators, the innovation strategy of PK-BN-PD screening quality control indicators mode was developed based on EMM. Complete the task will provide a reference model to quickly identify indicators of quality control of TCM based on the efficacy of TCM and provide new ideas for the establishment of the quality evaluation system for TCM.

英文关键词： efficacy material markers ;TCM injection;pharmacokinetic and pharmacodynamics;bayesian network;quality control compounets of TCM